A METAANALYSIS AND TRANSMISSION DISEQUILIBRIUM STUDY OF ASSOCIATION BETWEEN THE DOPAMINE D3 RECEPTOR GENE AND SCHIZOPHRENIA

We performed a meta-analysis of over 30 case-control studies of associ ation between schizophrenia and a bi-allelic, BalI polymorphism in exo n 1 of the dopamine D3 receptor gene. We observed a significant excess of both forms of homozygote in patients (P = 0.0009, odds ratio (OR) = 1.21, 95% Confidence Interval (CI) = 1.07-1.35) in the combined samp le of 5351 individuals. No significant heterogeneity was detected betw een samples and the effects did not appear to be the product of publis hing bias. In addition we undertook an independent, family-based assoc iation study of this polymorphism in 57 parent/proband trios, taken fr om unrelated European multiplex families segregating schizophrenia. A transmission disequilibrium test (TDT) showed a significant excess of homozygotes in schizophrenic patients (P = 0.004, odds ratio (OR)= 2.7 , 95% CI = 1.35-5.86). Although no significant allelic association was observed, a significant association was detected with the 1-1 genotyp e alone (P = 0.02, OR = 2.32, 95% CI = 1.13-4.99). In addition when th e results of the family-based association study were included in the m eta-analysis, the homozygosity effect increased in significance (P = 0 .0002, OR = 1.23, 95% CI = 1.09-1.38). The results of the meta-analysi s and family-based association study provide independent support for a relationship between schizophrenia and homozygosity at the BalI polym orphism of the D3 receptor gene, or between a locus in linkage disequi librium with it.